Monteiro C, Kasahara T, Sacramento PM, et al. - CXCR5, PD‐1 are expressed by circulating TFH (cTFH) cells; when activated, these cells express ICOS, and release IL‐21. Based on the production of IFN‐γ, IL‐4, and IL‐17 and expression of FoxP3, the following classification of these cells is done: cTFH1, cTFH2, cTFH17, and cTFR cells, respectively. For efficient humoral immunity, this CD4+T‐cell subset is significant, and pregnancy seems to favor IgG production. In this study, pregnancy enhanced the in vivo production of anti‐HBsAg IgG in HBV immunized women as well as there was direct correlation of the frequency of cTFH cells with estradiol levels. In vitro, direct increase in the percentage of different cTFH subsets was observed in correlation with pregnancy‐related dose of 17‐β‐estradiol (E2). While an increase in the proportion of differentiated TFH cells derived from naïve CD4+T‐cells was induced by E2 and progesterone (P4), amplification in the release of IL‐21 occurred only with using E2 in those cell cultures. In addition, E2 and P4 led to an increase in the proportion of memory B cells and plasma cells, respectively. In SEB‐activated B/TFH cell co‐cultures, the production of total IgG increased in correlation with using E2, in the presence of P4. Finally, among the hormones, P4 was noted to be stronger in upregulating the percentage of IL‐10+TFR cells. Togather, the results imply that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cTFH and B cell subsets.